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The objective of this thesis is to analyze the place of MRI-guided cryotherapy in the therapeutic strategy for recurrence of glioblastoma. Recurrence of glioblastoma, the most frequent primary malignant tumor in adults, is inevitable with a median survival rate of 8-9 months. Therefore, any new therapeutic modality represents an opportunity to improve survival. Oncologic cryoablation is performed by introducing, under radiological guidance, one or more cryoprobe (s) within a tumor process thus exposing it for a few minutes to extremely low temperatures. In addition, the procedure has been modernized to accurately apply cycles of the freezing and thawing phases. Four biological cellular injury mechanisms are induced and associated in time and space: direct or indirect cellular injury, vascular injury, apoptosis and immunomodulation. By its mechanism, cryotherapy could potentiate the effect of radiotherapy. Thus, a comparison of cryotherapy and radiotherapy treatments alone compared to their combination, on murine brain tumors grafted on immunocompetent mouse models was carried out. The results confirmed the potentiation of cryotherapy over radiotherapy with a significant difference in terms of survival in the radiotherapy combined with cryotherapy group compared to the other groups. The survival of six patients who received MRI-guided cryotherapy followed by microsurgical resection for recurrent glioblastoma was analyzed. We noted the absence of major complications. The overall follow-up was 30 months. The median progression-free survival and overall survival were 7.5 months and 22.5 months, respectively, and the 6-month progression-free survival rate was 50%. Radiological analysis in these 6 patients showed probable rupture of the blood brain barrier within an average of 2.83 months, confirmed by the results of the MRI with injection of gadolinium and by the perfusion sequence. All of this work opens up a new weapon in the management of recurrent glioblastoma by introducing cryotherapy into the existing therapeutic arsenal., Ce travail de thèse a pour objectif d’analyser la place de la cryothérapie guidée par IRM dans la stratégie thérapeutique de la récidive du glioblastome. La récidive du glioblastome, tumeur primitive maligne la plus fréquente chez les adultes est inéluctable avec une médiane de survie à la récidive de 8-9 mois. Par conséquent, toute nouvelle modalité thérapeutique représente une opportunité pour améliorer la survie. La cryothérapie à visée carcinologique ou cryoablation est effectuée en introduisant, sous guidage radiologique, une ou plusieurs cryosonde(s) au sein d’un processus tumoral l’exposant ainsi pendant quelques minutes à des températures extrêmement basses. En outre, la procédure s’est modernisée permettant d’appliquer avec précision des cycles de phases de congélation et de décongélation. Quatre mécanismes biologiques lésionnels sont induits et associés dans le temps et l’espace : lésion cellulaire directe ou indirecte, lésion vasculaire, apoptose et immunomodulation. Par ces mécanismes, la cryothérapie pourrait potentialiser l’effet de la radiothérapie. Ainsi, une comparaison des traitements de cryothérapie et radiothérapie seuls par rapport à leur combinaison, sur des tumeurs cérébrales murines greffées en ectopique sur des modèles de souris immunocompétentes a été réalisée. Les résultats confirment la potentialisation de la radiothérapie par la cryothérapie avec une différence significative en termes de survie dans le groupe radiothérapie combinée à la cryothérapie comparée aux autres groupes. La survie de six patients ayant bénéficié d’une cryothérapie guidée par IRM suivie d’une résection microchirurgicale pour une récidive de glioblastome a été analysée. L’absence de complication majeure était observée. La médiane de survie sans progression et de survie globale était respectivement de 7,5 mois et 22,5 mois et le taux de survie sans progression à 6 mois de 50%. L’analyse radiologique chez ces 6 patients a montré une probable rupture de la barrière hémato-encéphalique dans un délai moyen de 2,83 mois, confirmée par les résultats de l’IRM avec injection de produit de contraste et par la séquence de perfusion. L’ensemble de ces travaux permet d’ouvrir une nouvelle piste dans la prise en charge des récidives de glioblastome en introduisant la cryothérapie dans l’arsenal thérapeutique existant.

The role of cryotherapy in the treatment of pain has been known since the Egyptians. For fifty years, techniques initially dedicated to the whole body have evolved into more specific approaches by targeting nerve structures. Several indications for the treatment of acute and chronic pain have emerged and are supported by scientific evidence. A reduction in pain for up to several months, a decrease of opioid consumption and an improvement in the physical activity are among the main results reported in the literature. Cryotherapy appears to be an efficient treatment in pain management correlated with a relatively few numbers of side effects.

The role of cryotherapy in the treatment of pain has been known since the Egyptians. For fifty years, techniques initially dedicated to the whole body have evolved into more specific approaches by targeting nerve structures. Several indications for the treatment of acute and chronic pain have emerged and are supported by scientific evidence. A reduction in pain for up to several months, a decrease of opioid consumption and an improvement in the physical activity are among the main results reported in the literature. Cryotherapy appears to be an efficient treatment in pain management correlated with a relatively few numbers of side effects.Le rôle de la cryothérapie dans le traitement des douleurs est connu depuis l’époque des Égyptiens. Au cours des 50 dernières années, les techniques d’application systémique du froid ont évolué vers des approches plus ciblées visant les structures nerveuses. De nombreuses indications pour le traitement des douleurs aiguës et chroniques ont vu le jour et sont soutenues par des évidences scientifiques. Une diminution des douleurs jusqu’à parfois plusieurs mois, une baisse de la consommation d’opiacés ainsi qu’un gain fonctionnel sont parmi les résultats retrouvés dans la littérature. La cryothérapie est une option thérapeutique antalgique efficace comportant relativement peu d’effets secondaires.

The surgical management of breast cancer has been marked by a therapeutic de-escalation from radical surgery to breast conservation and from axillary curage to sentinel lymph node sampling. With regard to breast surgery, the de-escalation of treatment has been largely due to organized screening, which has made it possible to diagnose tumors of smaller volume or at an earlier stage. The indications for conservative surgery have been broadened by the addition of radiotherapy on one hand, and the introduction of adjuvant and neo-adjuvant treatments on the other hand. In an effort to de-escalate surgery, totally non-invasive techniques such as radiofrequency, HIFU (High Intensity Focused Ultrasound) or cryotherapy have been tested. Currently, three trials are underway to evaluate active surveillance, without surgery, in the management of certain low-risk ductal carcinomas in situ (DCIS). Regarding axillary procedures, the sentinel node technique has allowed axillary staging in patients with early breast cancer without clinical or radiological lymph node involvement. Currently, international recommendations (ASCO, NCCN) and the consensus of experts in St Gallen do not recommend additional curage in cases of macro or micrometastatic invasion of the sentinel lymph nodes if the criteria of ACOSOG Z0011 are met. The question now arises as to the relevance of a biopsy of suspected axillary nodes during the initial workup and the usefulness of the sentinel node technique in the case of a negative initial workup.

The objective of this thesis is to analyze the place of MRI-guided cryotherapy in the therapeutic strategy for recurrence of glioblastoma. Recurrence of glioblastoma, the most frequent primary malignant tumor in adults, is inevitable with a median survival rate of 8-9 months. Therefore, any new therapeutic modality represents an opportunity to improve survival. Oncologic cryoablation is performed by introducing, under radiological guidance, one or more cryoprobe (s) within a tumor process thus exposing it for a few minutes to extremely low temperatures. In addition, the procedure has been modernized to accurately apply cycles of the freezing and thawing phases. Four biological cellular injury mechanisms are induced and associated in time and space: direct or indirect cellular injury, vascular injury, apoptosis and immunomodulation. By its mechanism, cryotherapy could potentiate the effect of radiotherapy. Thus, a comparison of cryotherapy and radiotherapy treatments alone compared to their combination, on murine brain tumors grafted on immunocompetent mouse models was carried out. The results confirmed the potentiation of cryotherapy over radiotherapy with a significant difference in terms of survival in the radiotherapy combined with cryotherapy group compared to the other groups. The survival of six patients who received MRI-guided cryotherapy followed by microsurgical resection for recurrent glioblastoma was analyzed. We noted the absence of major complications. The overall follow-up was 30 months. The median progression-free survival and overall survival were 7.5 months and 22.5 months, respectively, and the 6-month progression-free survival rate was 50%. Radiological analysis in these 6 patients showed probable rupture of the blood brain barrier within an average of 2.83 months, confirmed by the results of the MRI with injection of gadolinium and by the perfusion sequence. All of this work opens up a new weapon in the management of recurrent glioblastoma by introducing cryotherapy into the existing therapeutic arsenal., Ce travail de thèse a pour objectif d’analyser la place de la cryothérapie guidée par IRM dans la stratégie thérapeutique de la récidive du glioblastome. La récidive du glioblastome, tumeur primitive maligne la plus fréquente chez les adultes est inéluctable avec une médiane de survie à la récidive de 8-9 mois. Par conséquent, toute nouvelle modalité thérapeutique représente une opportunité pour améliorer la survie. La cryothérapie à visée carcinologique ou cryoablation est effectuée en introduisant, sous guidage radiologique, une ou plusieurs cryosonde(s) au sein d’un processus tumoral l’exposant ainsi pendant quelques minutes à des températures extrêmement basses. En outre, la procédure s’est modernisée permettant d’appliquer avec précision des cycles de phases de congélation et de décongélation. Quatre mécanismes biologiques lésionnels sont induits et associés dans le temps et l’espace : lésion cellulaire directe ou indirecte, lésion vasculaire, apoptose et immunomodulation. Par ces mécanismes, la cryothérapie pourrait potentialiser l’effet de la radiothérapie. Ainsi, une comparaison des traitements de cryothérapie et radiothérapie seuls par rapport à leur combinaison, sur des tumeurs cérébrales murines greffées en ectopique sur des modèles de souris immunocompétentes a été réalisée. Les résultats confirment la potentialisation de la radiothérapie par la cryothérapie avec une différence significative en termes de survie dans le groupe radiothérapie combinée à la cryothérapie comparée aux autres groupes. La survie de six patients ayant bénéficié d’une cryothérapie guidée par IRM suivie d’une résection microchirurgicale pour une récidive de glioblastome a été analysée. L’absence de complication majeure était observée. La médiane de survie sans progression et de survie globale était respectivement de 7,5 mois et 22,5 mois et le taux de survie sans progression à 6 mois de 50%. L’analyse radiologique chez ces 6 patients a montré une probable rupture de la barrière hémato-encéphalique dans un délai moyen de 2,83 mois, confirmée par les résultats de l’IRM avec injection de produit de contraste et par la séquence de perfusion. L’ensemble de ces travaux permet d’ouvrir une nouvelle piste dans la prise en charge des récidives de glioblastome en introduisant la cryothérapie dans l’arsenal thérapeutique existant.

Professional tennis generates a high-level of fatigue due to an important training load but also by the schedule of the professional circuit (ATP, WTA). In addition to the nomadic nature of the tennis tour, players are often required to complete competitive matches and training sessions with an inadequate timeframe to recover well. The adequate management of induced fatigue and recovery allows tennis players to perform during competition but also plays a key role in the avoidance of under-recovery, illness, and injury during preparatory and pre-competitive phases. Recovery must be fine-tuned, especially regards to training-induced fatigue which depend on the context (sport, training period, type of fatigue, athlete ‘status). Cryotherapy is now a popular recovery method among tennis players. However, these cold recovery methods are applied empirically while little research have been done on the efficiency of cryotherapy depending on the context. However, no studies have demonstrated the potential effect of whole-cryotherapy (WBC) and cold-water immersion (CWI) on induced elite tennis fatigue and recovery. Therefore, it is necessary to demonstrate the effectiveness of each recovery technique to determine how it can effectively improve the athlete ‘recovery. The first study aims to examine, during 15 consecutive months, the training type clusters, and recovery practices adopted by elite tennis players under ecological training conditions. The respective impacts of training type clusters and recovery techniques on subjective variables, which reflect the players' recovery perceptions, were subsequently determined. Results showed that perceived recovery was not sensitive to training clusters or the associated acute training load. However, cooling strategies were relevant for the alleviation of tennis training-induced soreness (12h-16h post-training). The second study compared the effect of WBC and CWI of the accumulated fatigue induced by three consecutive days of simulated tennis matches. Results shows that a 1.5 hour simulated tennis match leads to modest structural impairments, neuromuscular function alterations without decline in specific and non-specific performance. These impairments were completely recovered within 24 h and were not exacerbated by consecutive matches. However, three consecutive tennis matches induce a moderate increase in muscle soreness which was attenuated by CWI and WBC recovery techniques. In a practical view, when a player competing tournaments (on fast surfaces), the daily use of CWI and WBC could be helpful to attenuate muscle soreness.; L’organisation du circuit professionnel impose actuellement au joueur de tennis de haut niveau une planification annuelle des entraînements et des compétitions très dense. Ainsi, une gestion appropriée et équilibrée de la fatigue et de la récupération apparait primordiale afin de permettre au joueur de tennis élite d’être performant lors des compétitions mais aussi d’éviter la survenue d’épisodes de fatigue sévère, de surmenage, de blessures ou de maladies. Les connaissances issues de la littérature scientifique incitent à adapter et planifier spécifiquement la récupération en fonction du contexte (discipline, période d’entraînement, type de fatigue, statut de l’athlète). Pourtant, les joueurs ont actuellement recours de façon relativement empirique à des stratégies de récupération diverses, incluant l’application de froid. Cependant, peu d’études se sont intéressées aux effets de ces méthodes de récupération sur les réponses à la charge induite par le tennis pratiqué à haut niveau. Il semble nécessaire de déterminer l’efficacité de chaque technique de récupération dans ce contexte afin d’identifier quelles stratégies répondent le mieux à la nécessité de récupérer. La première partie de ces travaux de thèse a donc eu pour objectif de décrire, sur une période de 15 mois et dans un cadre écologique, les contenus et la charge de travail induite par l’entraînement, les pratiques de récupération et leurs impacts sur la fatigue subjective des joueurs de tennis élites. À court terme, il apparait que les contenus d’entraînement, regroupés et leur charge associée n’impactent pas différemment la fatigue perceptive rapportée. Au sein des stratégies de récupération utilisées par les joueurs, les techniques par le froid (cryothérapie corps entier, immersion en eau froide, bain contrasté) sont les plus représentées. Les modèles statistiques utilisés montrent que ces techniques de récupération par le froid sont les seules associées à une diminution significative des sensations de douleurs musculaires 12-16h post-entraînement. Notre seconde étude a comparé l’efficacité de ces différentes techniques de récupération par le froid dans des conditions de fatigue accumulée, simulant celles induites lors de compétitions professionnelles de tennis. Ces travaux montrent que l’enchaînement de trois jours de matchs de tennis d’1h30, induit une fatigue significative mais modérée. En effet, les paramètres de fatigue neuromusculaire (centrale et périphérique), physiologique diminuent significativement lors du premier jour, mais ne sont pas modifiés en réponse aux matchs de tennis des jours suivants. Au cours des quatre jours de protocole, l’immersion en eau froide et de la cryothérapie corps entier permettent de limiter l’augmentation des sensations de douleurs musculaires. Ces résultats valident l’intérêt d’utiliser les techniques de récupération par le froid pour diminuer les sensations de douleurs musculaires de joueurs de tennis élites en période d’entraînement. Dans le cadre précis de compétitions réalisées sur surface dure (hors Grands Chelems), l’utilisation quotidienne des techniques de récupération par le froid seront alors conseillées pour limiter l’accumulation des sensations de douleurs musculaires.

Whole body cryotherapy is mainly performed either by immersion in cold water or in a cryotherapy chamber. Practiced since Antiquity and considered as a « natural » method, cryotherapy is attracting more and more followers. Beneficial health effects have been described in the literature. However, interpretation of its effects is difficult due to low quality of current studies. Cryotherapy could however be useful in addition to conventional therapies in various pathologies and situations, provided that the risks, contraindications and rules of good practice are known.La cryothérapie du corps entier se pratique principalement soit par immersion en eau froide, soit en chambre de cryothérapie. Pratiquée depuis l’Antiquité et considérée comme une méthode « naturelle », la cryothérapie tend à attirer de plus en plus d’adeptes. Des effets bénéfiques pour la santé ont été décrits dans la littérature. Néanmoins, l’interprétation de ses effets est difficile en raison de la faible qualité des études actuelles. La cryothérapie pourrait toutefois être utile en complément des thérapies classiques dans diverses pathologies et situations, à condition de connaître les risques, les contre-indications et les règles de bonnes pratiques.

In 2030, the European Union will include 14 to 17 million atrial fibrillation (AF) patients, with 120,000 to 215,000 new cases each year. The increase in the prevalence of this arrhythmia has led to the development of new therapeutic intervention strategies to manage the different aspects of this disease. Thus, endocavitary or epicardial ablation of AF, by radiofrequency or cryoablation, provides superior results to antiarrhythmic therapy in controlling symptoms and preventing heart failure in paroxysmal or persistent AF. In heart failure patients with advanced AF, the ablation of the atrioventricular junction associated with the implantation of a bi-ventricular pacemaker has just demonstrated its clear superiority, bringing this technique up to date. Finally, in the event of a major bleeding risk and contraindication to anticoagulants, percutaneous occlusion of the left atrium has proven its value in preventing AF-related embolic events. The future will certainly see the emergence of new technologies but also personalized strategies based on an optimal selection of the right candidates for these interventions, thanks in particular to the contribution of imaging before the procedure.

Cyclodialysis is a rare condition that is difficult to manage. We present the case of a woman with a cyclodialysis complicated by chronic hypotony requiring two surgeries to achieve reattachment of the ciliary body. We also report the results of a review of the literature regarding the treatment of this condition.This is a 46-year-old woman with history of trauma to the right eye. Examination revealed an intra-ocular pressure (IOP) of 7mmHg, a shallow anterior chamber and signs of chronic hypotony on fundus examination (vascular tortuosity, hypotony maculopathy) due to an extensive 360° cyclodialysis, confirmed by ultrasound biomicroscopy. Transcleral cryotherapy as a first-line approach did not achieve reattachment of the ciliary body. Secondary pars plana vitrectomy with gas tamponade (C2F6) reattached the ciliary body and restored the intraocular pressure (12mmHg) and normal fundus appearance. The patient recovered corrected visual acuity of 20/20.To our knowledge, there is no standardized management for cyclodialysis. The study of the literature available on the Medline database showed that direct cyclopexy remains the most common treatment, followed by vitrectomy with internal tamponade. Neither the extent nor the duration of the cyclodialysis can predict the visual recovery, which can be major even after weeks of hypotony.The management of cyclodialysis is not well-defined; it remains a true therapeutic challenge.

Chromomycosis is a chronic fungal skin infection, mainly affecting the limbs. It is responsible for severe morbidity and its treatment remains long and disappointing. Rarely described in Morocco, we report a new observation that has evolved very well under treatment combining terbinafine and cryotherapy over a short duration.A 56-year-old patient, immunocompetent, had a pustular and crusty placard on both forearms that had evolved for a year. Mycological examination showed fumagoid bodies and cutaneous biopsy showed epithelioid granulomas and giant cells without necrosis. The PCR confirmed a chromomycosis at Fonsecaea pedrosoi. HIV serology was negative. Treatment with terbinafine 250mg/d for 6months combined to cryotherapy resulted in complete remission with initial clinical improvement after only 3 weeks.Chromomycosis occurs increasingly in non-tropical areas. If diagnostic methods become more effective, management remains difficult and poorly codified. Terbinafine-cryotherapy combination would bring a lot of benefits with a little risk to bothpractitioner and patient.This combined treatment would constitute an excellent therapeutic alternative because of its efficiency, feasibility, low cost, method of administration and aesthetic result.

Retinal hemangioblastoma (RH) is a benign vascular tumor frequently associated with Von Hippel-Lindau disease (VHL). Tumor growth of RH may lead to deterioration of visual acuity, which can be difficult to treat. Early diagnosis may reduce complication rate and side effects of treatment. The present retrospective study evaluates the long-term follow-up and complications of RH treatment as a function of the therapeutic strategy used.The study included patients with RH, followed at Croix Rousse university hospital, Lyon between 2010 and 2017. The following clinical features were recorded : age at diagnosis, presenting symptom, presence of VHL disease, treatments used, post-therapeutic complications and visual outcomes.Seven eyes of five patients were included in our study. Eighty percent of the patients had a mutation in the VHL gene. Four eyes (57%) were treated with laser photocoagulation and three eyes (43%) were treated with cryotherapy. The mean duration of follow-up was 35 months. One of the eyes treated using laser photocoagulation was complicated by an early epiretinal membrane with no visual consequence. Of the eyes treated by cryoapplication, one was complicated by a vitreous hemorrhage, and another by a rhegmatogenous retinal detachment, both of which resulted in a decrease in visual acuity.The long-term outcome for patients treated for RH was relatively good. Complications were strongly correlated with the initial size of the vascular tumor. Early diagnosis seems to improve visual outcomes. Ophthalmologic monitoring should be part of the systemic, multidisciplinary management.

Conjunctival-pigmented tumors are rare, but they are one of the most commonly encountered by the pathologist working with the department of ophthalmology. Nevus and melanoma can be encountered and have some histological difference compared to their cutaneous counterpart. Primary acquired melanosis (PAM) is a conjunctival specific entity. This clinical term includes several histological lesions ranging from benignity to melanoma precursor lesion. Histologic examination determines the therapy and the risk of progression to melanoma. We present here a histopathological, clinical and therapeutic synthesis of conjunctival-pigmented lesions, emphasizing the importance of a good understanding between clinicians and pathologists.

Pain management is not limited to the putting in place of pharmacological, surgical, physiotherapy or psychological strategies. Non-pharmacological therapies can also be proposed, notably in relation to chronic pain. Appreciated by patients and developed by caregivers, they require appropriate regulatory guidelines and specific training in order for them to be implemented safely.

Increasing numbers of reports of rapidly arising, isolated or eruptive keratoacanthomas (KA) and squamous cell carcinomas (CSC) on the red part of tattoos tend to suggest a non-fortuitous link with the procedure. We report herein two different presentations of KAs on tattoos: one patient with multiple eruptive KAs on sun-exposed areas of a recent red tattoo and another with a solitary lesion on a recent tattoo. We discuss the issues related to the distinction between KAs and CSCs in this particular context.Case No. 1: A 55-year-old heavily tattooed man presented multiple round keratotic verrucous-like lesions restricted to a red tattoo. The tattoo had been performed by a professional tattooist in summer 2016, a week before the onset of the symptoms. The patient did not protect a part of his tattoo from sun-exposure during the healing phase and lesions developed only on the sun-exposed tattooed parts. In January 2017, he consulted with about ten lesions. The histologic study by shaving of a lesion militated in favor of a CSC, KA type. The physical examination was unremarkable. He had no previous history of skin cancer. Two weeks later, most of the lesions regressed spontaneously. Based on the clinical history and progression of the lesions, a diagnosis was made of eruptive KA on a red tattoo. Residual lesions were treated by cryotherapy or excision. Case No. 2: A 72-year-old woman developed a 1-cm painful dome-shaped nodule with a central crust three weeks after tattooing. Full excision confirmed the diagnosis of KA.To date, we have found 31 case reports and series (17 men, median age: 50.5 years) of KA and CSC on tattoos. Lesions usually develop rapidly after completion of the tattoo, after between one week and several months. Exceptional cases have been described in old tattoos. Red tattoo ink is most commonly the culprit. The main difficulty lies in distinguishing between KA and CSC. Nowadays pathologists agree that a KA should be considered as a variant of CSC. Eruptive forms of KA present a peculiar situation. They may sometimes be inherited, and KA on recent traumatized areas or drug-induced have been described. Like other authors, we believe that cases of CSC on red tattoos belong rather to the KA type. The physiopathogenesis of tattoo-associated eruptive KA and CSC is not clearly understood, but could be multifactorial, involving: the trauma induced by tattooing, local inflammatory reaction, a component of the red ink, external factors such UV exposure, and a possible genetic predisposition. Rapidly arising KA and eruptive KA on top of recent (red) tattoos are not fortuitous. The lesions should be excised and the patient monitored. Additional studies on tumor specimens are warranted to identify the possible causative agents in tattoo ink that may be responsible for such reactions.

Percutaneous lung thermo-ablation has steadily been developed over the past 15years. Main indications are early stage non-small cell lung carcinoma (NSCLC) for non-surgical patients and slow evolving localized metastatic disease, either spontaneous or following a general treatment. Radiofrequency, being the most evaluated technique, offers a local control rate of about 80-90% for tumors3 cm in diameter. With excellent tolerance and very few complications, radiofrequency may be proposed for patients with a chronic disease. Other ablation techniques under investigation such as microwaves and cryotherapy could allow overcoming radiofrequency limits. Furthermore, stereotactic radiotherapy proposed for the same indications is efficient. Comparative studies are warranted to differentiate these techniques in terms of efficacy, tolerance and cost-effectiveness.

Cryotheapy i widely and empirically used in an adjuvant setting in inflammatory rheumatic diseases, with a low level of evidence. We performed a systematic review of the literature and, by pooling data from 6 non-controlled studies, we could show that local cryotherapy (local or whole-body cryotherapy) applaied twice a day for 7-15 days significantly reduced the pain VAS and the DAS28 activity score in rheumatoid arthritis. Furthermore, local cryotherapy (ice packs or cold gas) showed significantly greater intra)class effect-sizes compared to whole-body cryotherapy. The aim of this work was to measure the effects of local cryotherapy on pain, synovial and systemic inflammation in arthrici patients and in the murine model of adjuvant-induced arthritis. First, in the CDRI and ALGGAR randomized studies, we evaluated the effects of 2 local cold applications (ice versus cold gas) on pain, power Doppler activity and intra-joint cytokine protein levels in 46 patients suffering from non-septic knee arthritides. Contralateral arthritic knee were used as control. Secondly, we studied the in vitro effects of mild hypothermia (30°C for 2 hours) on cytokine protein expression in a model of cultured arthritic rat patellae. Thidly, we studied the in vitro effects of sub-chronically applied ice or cold gas (twice a day for 14 days versus non-treated arthritic controls) on the arthritis score, the ankle diameter, pro-inflammatory cytokine gene transcription levelsin hind paws (Q-RT-PCR) and cytokine plasma protein levelx (Multiplex and ELISA) after 14 days of treatment. In the CDRI study, local cryotherapy (ice and cold gas) significantly reduced the pain VAS and the power Doppler score in treated kness, and these effects remained significant the day afetr 2 cold applicaitions. In an intermediate analysis of the ALGGAR study results, by pooling the 2 treatment groups, we could show significant decreases in IL-6 protein, IL-1β and VEGF synovial fluid protein levels after 2 cold applicatios. In arthritic rat patella explangt culture experiments, punctual hypothermia significantly reduced IL-6 protein levels. In vivon ice was more efficient on the clinical parameters and better tolerated compared to cold gas. Both techniques significantly reduced IL-6, IL-17A ans IL-1β gene transcription levels in hind paws after 14 days of treatment. Both techniques redcued IL-17A plasma protein levles, while ice also reduced IL-6 and VEGF plasma protein levels. Conversely, we observed no effect of local cryotherapy on the TNF-α pathway, neither in patients nor in our animal model. Here we demonstrate for the first time therapeutic and anti-inflammatory effet-cts of local cryothepary in arthritis. The biological effects were IL-6/IL-17-driven and TNF-α independent. Further studies will help elucidate the underlying molecular mlechanisms involved and detemrine whether local cryotherapy might be a safer alternative to NSAIDs ans corticosteroids in inflammatory rheumatic diseases.; La cryothérapie est utilisée de manière large et empirique à visée adjuvante dans les rhumatismes inflammatoires, avec un niveau de preuve faible. Dans une revue systématique de la littérature, en poolant les données de 6 études non contrôlées, nous avons pu démontrer que la cryothérapie (locale ou corps entier) appliquée deux fois par jour pendant 7 à 15 jours réduisait significativement l'EVA douleur et le score d'activité DAS25 dans la polyarthrite rhumatoïde. La cryothérapie locale (glace ou gaz froide) montrait par ailleurs des effets taille intra-classes supérieurs à ceux obtenus en utilisant la cryothérapie corps entier. L'objectif de ce travail était de mesurer les effets de la cryothérapie locale sur al douleur, l'inflammation synoviale et systémique chez les patients arthritiques et dans le modèle murin d'arthrite à l'adjuvant. Dans les études randomisées CDRI et ALGGAR, nous avons évalué les effets de deux applications locales de froid (glace versus gaz froid) sur la douleur, l'activité Doppler et les taux protéiques de cytokines intra-articulaires controlatéraux non souffrant d'arthrites de genou non septiques. Les genoux arthritiques controlatéraux non traités étaient utilisés comme contrôles. Nous avons par ailleurs étudié in vitro les effets de l'hypothermie modérée (30°C pendant 2heures) sur l'expression protéique des cytokines dans un modèle de culture de rotules de rats arthritiques. Nous avons enfin étudié in vitro dans l'arthrite à l'adjuvant les effets de l'application sub-chronique de glace ou de gaz froid (2 fois par jour pendant 14 jours versus contrôles arthritiques non traités) sur le score d'arthrite, le diamètre de cheville, la transcription des gènes codant pour les cytokines pro-inflammatoires dans les pattes arrières (Q-RT-PCR) et l'expression protéique des cytokines dans le plasma (Multiplex et ELISA) après 14 jours de traitement. Dans l'étude CDRI, la cryothérapie locale (glace et gaz froid) réduisait significativement l'EVA douleur ainsi que le score Doppler dans les genoux traités, ces effets persistant le lendemain des deux applications. Dans une analyse intermédiaire des résultats de l'étude ALGGAR, en combinant les deux groupes de traitement (glace et gaz de froid), nous avons observé une baisse des taux d'IL-6, d'IL-1β et de VEGF dans le liquide articulaire arès deux applications. dans les cultures d'explants de rotules de rats arthritiques, l'hypothermie ponctuelle réduisait significativement les taux d'IL-6, IL-17A et IL-1β dans les pattes arrières après 14 jours de traitement. Les deux modalités réduisaient significativement les niveaux plasmatiques d'IL-17A et la glace réduisait en outre les taux d'IL-6 et de VEGF. Nous n'avons observé aucun effet de la cryothérapie locale sur le voie du TNF-α chez l'homme ni chez l'animal. Nos résultats démontrent pour la première fois un effet thérapeutique et anti-inflammatoire de la cryothérapie locale dans l'arthrite. Les effets biologiques était IL-6/IL-147 dépendants et TNF-α indépendants. Des études complémentaires permettront de mieux caractériser les mécanismes moléculaires sous-jacents et de déterminer su la cryothérapie locale pourrait être une alternative aux AINS et corticoïdes dans les rhumatismes inflammatoires.

This thesis has been completed as part of a CIFRE agreement between the research and development department of the Cryantal Company (Lognes, France) and the C3S (EA4660) and MOVE (EA6314) laboratories from the Universities of Franche-Comté and Poitiers. The aim of the thesis was the development of a new technology of whole-body Cryotherapy (WBC) chamber. The various studies that we conducted centred on : – the identification of technological and methodological requirements from field studies and the analysis of scientific literature; – the development of a WBC chamber prototype according to the identified requirements; – the technological validation of the prototype to its industrialization; and – the evolution of the prototype toward a marketable version. The thesis was divided into two parts. The first part highlights the practical applications and the technological requirements to identify the limits and the advantages of the existing methodologies and technologies in order to develop a new WBC chamber device. Studies performed in the field during competitions showed that WBC is well tolerated by athletes and can be used during heavy competition periods and/or during training periods. We also demonstrated that female athletes with lower body-mass indexes seem to be much more sensitive to cold than female athletes with higher body-mass indexes. The literature review reported a lack of data concerning the actual temperature inside the WBC chamber and cabin. The lack of methodological information for the exposure protocol was also pointed out. It creates the link between the field of application of the WBC and the different technology used. The second part presents the technological development of the new WBC chamber prototype, its validation, and its optimisation in order to be commercialized. This part includes a validation study of the prototype based on the effects of a 3-minute exposure on the skin temperature decrease of exposed individuals. The results showed a similar decrease to those observed with other WBC existing technologies. This is certainly due to the homogeneity of the temperature of exposure and the new technology developed. Preliminary measurements of the prototype allowed for the prospect of the commercialization of this new WBC chamber.; Cette thèse a été effectuée sous le couvert d’une convention CIFRE issue d’une collaboration entre la Société Cryantal (Lognes, France) et les laboratoires universitaires C3S (EA 4660) et MOVE (EA 6314) de Franche-Comté et de Poitiers. Elle a été articulée autour du développement d’une nouvelle technologie de chambre de Cryothérapie Corps Entier (CCE). Le travail mené au cours de ces quatre années a eu pour objectifs : 1) L’identification des besoins technologiques et méthodologiques à partir d’études conduites sur le terrain et de l’analyse de la littérature scientifique ; 2) Le développement d’un prototype de chambre CCE à partir des besoins identifiés ; 3) La validation technologique du prototype en vue de son industrialisation ; 4) D’apporter des perspectives d’évolutions futures pour le développement du prototype afin qu’il devienne une chambre CEE commercialisable. Afin de répondre à ces objectifs, la thèse a été divisée en deux parties distinctes.La première partie met en évidence les applications pratiques et les besoins technologiques afin d’identifier les limites et avantages des différentes méthodes et techniques utilisées en vue du développement d’un nouveau prototype de chambre CCE. Les études conduites sur le terrain dans les conditions réelles de compétition ont montré que la CCE n’était pas vécue comme une contrainte importante par les athlètes et qu’elle leur permettait d’améliorer la qualité de leur sommeil perçu. Nous avons également montré que des individus avec un indice de masse corporel moins élevé supportaient moins bien les expositions au froid extrême en cabine comparé à ceux possédant un indice de masse corporel plus important. La revue de littérature scientifique a mis en évidence le manque crucial de données valides concernant les températures d’exposition dans les chambres et cabines. Elle pointe également pour la première fois, l’ensemble des protocoles d’expositions utilisés à ce jour dans les domaines d’applications relatifs aux pathologies traumatiques et de récupération physique. Elle crée le lien indispensable entre les différents domaines d’utilisation de la CCE et les différentes technologies utilisées.La seconde partie expose l’ensemble du développement technologique du prototype de la nouvelle chambre CCE, sa validation et son optimisation pour pouvoir prétendre à sa commercialisation. Elle comporte une étude scientifique de validation technologique du prototype de chambre de CCE basé sur la variation de la température cutanée des individus exposés. Les résultats ont montré que les variations de température cutanée engendrées par l’exposition avec la nouvelle technologie étaient similaires aux variations rapportées avec les autres technologies existantes. Les mesures préliminaires réalisées sur le prototype ont permis d’apporter des perspectives d’évolutions futures en vue de la commercialisation de la chambre.

Following competition, athletes commonly use strategies to accelerate their recovery from muscle damage. The overall objective of this thesis was to study the effects of different recovery strategies on recovery kinetics following exercise-induced muscle damage. The aims of the studies were as follows: 1) to compare the effects of cold-water immersion (10 minutes at 10°C) and whole-body cryotherapy (3 minutes at -110°C), 2) to assess the effects of an upper-limb strength training session, performed the day after a lower-limb exercise,, 3) to study the effects of a placebo ingestion in comparison with a passive recovery. The experimental model used to induce muscle damage in these three studies consisted of 5 sets x 15 repetitions of maximal eccentric contractions of the knee flexors muscles. This exercise resulted in a decrease of muscle function, increases in blood creatine kinase concentration as well as increases in perceived muscle soreness. Muscle function blood markers and subjective recovery from muscle damage were assessed throughout a 72h period post exercise. In the first study, cold-water immersion was more effective than whole-body cryotherapy evidenced through an accelerated recovery of both single and double leg countermovement jump 72h following exercise. In the second study, the upper-limb strength training session had a moderate beneficial effect on concentric force recovery 48h after the exercise and both interestingly and importantly, did not have any detrimental effect on recovery. Finally for the third study, placebo ingestion was ‘very likely’ to have a beneficial effect on jump performance and muscle soreness 72h post-exercise. Additionally, perceived recovery was moderately better 72h following exercise. In conclusion, the studies conducted in this thesis showed that the recovery strategies of cold-water immersion, strength training and ingestion of a placebo, may be effective after exercise-induced muscle damage., Après une compétition, certains sportifs utilisent des stratégies pour accélérer la récupération des dommages musculaires. Le but général de cette thèse était d’étudier les effets de différentes stratégies sur les cinétiques de récupération après un exercice inducteur de dommages musculaires. Les objectifs des études réalisées étaient : 1) de comparer les effets du bain froid (10 minutes à 10°C) et de la cryothérapie corps entier (3 minutes à -110°C) sur la récupération ; 2) d’évaluer les effets d’une séance de musculation du haut du corps réalisée le lendemain d’un exercice des membres inférieurs sur leur récupération; 3) d’étudier les effets de la consommation d’un placebo en comparaison avec une condition contrôle sur les cinétiques de récupération. Le modèle expérimental utilisé pour induire des dommages musculaires dans ces trois études était un exercice constitué de 5 séries de 15 contractions excentriques maximales des fléchisseurs du genou. Cet exercice était caractérisé par une baisse de la fonction musculaire, une augmentation des concentrations sanguines en créatine kinase et une augmentation des douleurs musculaires. La fonction musculaire, des marqueurs perceptifs et sanguins des dommages musculaires étaient également évalués au cours des 72h suivant cet exercice. Dans la première étude, le bain froid permettait d’accélérer la récupération de la performance lors d’un saut en contre-mouvement sur une jambe et sur deux jambes 72h après l’exercice en comparaison avec la cryothérapie corps entier. Dans la deuxième étude, la musculation du haut du corps n’avait pas d’effet délétère sur la récupération et avait un effet bénéfique modéré sur la récupération de la force concentrique 48h après l’exercice. Dans la troisième étude, la consommation d’un placebo présentait une très forte probabilité d’avoir un effet bénéfique sur la performance en saut et les douleurs musculaires 72h après exercice. La perception de la récupération était également modérément améliorée 72h après exercice. En conclusion, les trois stratégies de récupération utilisées lors de ces études à savoir le bain froid, la séance de musculation et la consommation d’un placebo peuvent être efficaces après des exercices induisant des dommages musculaires.

Chromomycosis, or chromoblastomycosis, is caused by cutaneous inoculation of dematiaceous fungi of telluric or plant origin. It is generally seen in tropical or subtropical zones. Treatment of the condition is known to be complex. Herein we report a case of chromomycosis contracted in a temperate region of Eastern Europe/Central Asia that was effectively treated with oral itraconazole and terbinafine in combination with cryotherapy.A 44-year-old immunocompetent male subject consulted for a lesion on the buttocks that he had sustained 16 years earlier, and which, although never previously treated, had only become troublesome within the last few months. The examination revealed a large erythemato-squamous plaque containing a heterogeneous infiltrate. The diagnosis was based upon biopsy, with histological examination revealing sooty mould ; culture of a second sample showed the causative agent to be Fonsecaea pedrosoi. After 30 months of treatment combining oral terbinafine at a very high dose (1000mg/day), topical terbinafine and adjuvant cryotherapy, considerable, though incomplete, improvement was obtained. Finally, combined use of terbinafine (500mg/day) and itraconazole (200mg/day) led to clinical and histological cure.The possibility of acquiring chromomycosis other than in a tropical zone is slight but has nevertheless been described, particularly in Eastern Europe. In our patient, the exact source of contamination is unknown, although it may have been acquired through frequent horse-riding or use of saunas. This case confirms the efficacy of combined itraconazole and terbinafine against this condition, which is usually difficult to treat.

Retrospective study analyzing clinical characteristics and treatment of children affected by Leber-Coats' disease.Children with Leber-Coats' disease seen in Edouard-Herriot Hospital, Lyon, between January 2004 and September 2013 were included. The following clinical characteristics were reported: sex, age at diagnosis, presenting symptom, Shields' stage, treatment used, and visual outcomes.Ten children were included in our study. Mean age at diagnosis was 5.5 years. The disease was unilateral in 9/10 cases. The presenting symptom was loss of vision in 7/10 cases, strabismus in 3/10 cases, and microphthalmos in 1 case. The diagnosis was made fortuitously during a follow-up of familial congenital cataract in 2 patients. No cases of leukocoria were seen. Shields' stages were distributed as follows: stage 1, 2A and 2B: 1 case each, stage 3A1: 7 cases, stage3A1: no cases. Laser photocoagulation was used up to stage 2B, combined with cryotherapy in stage 3A. Stage 1 and 2A were associated with relatively good final visual acuity. Significant macular lipid exudate (stage2A) was associated with a worse prognosis.These epidemiological data help us to better characterize these patients' prognosis. Early diagnosis seems to improve visual outcomes.

Since 2007 in France, human papilloma virus (HPV) vaccination has been licensed for use as a vaccine against HPV 6, 11, 16 and 18. The impact on the epidemiology of external genital warts (EGWs) in a large population remains unclear.To determine epidemiologic and clinical features of patients presenting EGWs in France in the era of HPV vaccination.In this prospective, observational study, we analyzed clinical features and treatments between January 1st, 2012 and March 31, 2012 for patients consulting for EGWs at 15 STI clinics throughout France.A total of 372 men and 111 women were included; mean age 31.2 years. The women were younger than the men (31.7 and 28.9 years respectively P0.05). Among the patients, 416 (85.7%) were heterosexual, 13 bisexual and 54 (11.2%) homosexual, including one female. Males reported more sexual partners in the last 12 months (more than 3 partners in 32.6% versus 11.9%, P0.01). Among the men, 230 had involvement of the penis alone and 46 had involvement of the anus alone. Seventy-six patients had EGWs of the anus, and of these 26 were MSM. In females, 76 had an infection of the vulva alone and 22 co-infection of the vulva and anus. MSM and females were at higher risk than heterosexual males for anal involvement (P0.0001 and P=0.004, respectively). Three women had been vaccinated: two with GardasilWith the advent of HPV vaccination, a global strategy for the prevention and treatment of EGW should be implemented.